Method of dissolving an obstruction in a vessel

ABSTRACT

A method of dissolving an obstruction in a blood vessel by the steps of preventing blood which is in contact with the obstruction from flowing through the vessel to locations downstream of the obstruction while permitting blood to flow through a passage past the obstruction; delivering to the obstruction a dissolution agent which works in conjunction with blood components to effect dissolution of the obstruction; analyzing the composition of fluid in contact with the obstruction; and at least periodically supplying blood to the fluid in contact with the obstruction, based on the result of the analyzing step.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a division of U.S. application Ser. No. 07/492,582 filed Mar.13, 1990 now U.S. Pat. No. 5,090,960, itself a continuation-in-part ofU.S. application Ser. No. 07/464,029 filed Jan. 12, 1990, now abandoned.

BACKGROUND OF THE INVENTION

The present invention relates to the treatment of obstructions in ablood vessel, and particularly the elimination of such obstructions bychemical dissolution.

The formation of a blood clot in the cardiovascular system usuallyrequires prompt medical intervention, and this is particularly true inthe case of arterial blood clots, most particularly those in a coronaryartery, since such clots can be life threatening. Obstructions formed ofother materials, such as plaque and fibrin, can also require medicalintervention.

Various techniques for removing such obstructions are known, thesetechniques generally involving surgical intervention or the delivery ofa dissolution agent, e.g., a thrombolytic agent.

In principle, the use of a thrombolytic agent offers the advantage ofavoiding the physical trauma associated with surgical intervention.However, the techniques typically employed to deliver thrombolytic agentto the site of a clot are somewhat complex and/or require theintroduction of a considerable quantity of thrombolytic agent into theblood stream in view of the fact that such agent is entrained in theblood stream and thus carried away from the site of the clot, unless theclot is completely blocking the vessel. Since thrombolytic agents areforeign substances to the patient's body, the larger the quantity ofsuch agent introduced into the blood stream, the greater the danger ofadverse side effects and the greater the cost. In addition, if largequantities of agent are introduced into the blood stream, the resultcould be that subsequent surgical intervention which might otherwise beindicated could not be performed. Similar considerations apply to othertypes of dissolution agents.

U.S. Pat. No. 4,423,725, which issued to O. E. Baran on Jan. 3, 1984,describes an intervention device composed of a catheter having a bloodflow lumen, a chemical delivery lumen and a suction lumen, associatedwith two annular cuffs which are inflatable to isolate a blood vesselregion containing an obstruction. This patent discloses the treatment ofblood vessel obstructions by balloon angioplasty followed by theapplication of anticoagulant drugs or cholesterol diluting drugs.

SUMMARY OF THE INVENTION

It is therefore an object of the present invention to dissolveobstructions in a blood vessel in a minimum of time and whileintroducing a minimum of dissolution agent into the blood vessel.

Another object of the invention is to effect dissolution by a simple andreadily controllable procedure which allows, particularly, control ofthe relative concentrations of dissolution agent and blood at thetreatment site.

Still another object of the invention is to permit reliable verificationthat the dissolution agent is being delivered precisely to the site ofthe clot.

Yet another object of the invention is to facilitate the delivery anX-ray detectable dye to the clot site.

The above and other objects are achieved, according to the presentinvention, by a device for performing regional perfusion obstructiondissolution, comprising:

an infusion catheter insertable into a blood vessel to extend across thesite of a clot, the infusion catheter having a length and extending inthe direction of the length between a distal end via which the infusioncatheter is inserted into the blood vessel and a proximal end remotefrom the distal end, and the infusion catheter being configured to have:

first flow means defining a blood bypass flow path extending along aportion of the length of the infusion catheter and communicating withregions surrounding the infusion catheter at first and second locationsalong the length of the infusion catheter such that when the infusioncatheter extends across an obstruction site in a blood vessel, the firstand second locations are positioned upstream and downstream,respectively, of the obstruction with respect to the direction of bloodflow in the vessel; and

second flow means defining a dissolution agent flow path extending alongthe length of the infusion catheter from the proximal end andcommunicating with a region surrounding the infusion catheter at a thirdlocation along the length of the infusion catheter between the first andsecond locations for delivering dissolution agent to the obstructionwhen the infusion catheter extends across the obstruction site in theblood vessel;

a suction catheter insertable into the blood vessel and positionable atthe obstruction site independently of the infusion catheter and havingproximal and distal ends and a suction lumen extending between theproximal and distal ends;

first blocking means carried by the infusion catheter at a fourthlocation between the first and second locations and spaced from thethird location to be located at one side of the obstruction site whenthe infusion catheter is inserted into the blood vessel; and

second blocking means carried by one of the catheters at a position tobe located at the other side of the obstruction site at least when bothof the catheters are positioned at the obstruction site; wherein

both of the blocking means are controllable for blocking blood flowthrough the vessel along a path exterior to the catheters.

The objects according to the invention are further achieved by using thedevice defined above in the following manner:

introducing the catheters into a blood vessel containing an obstructionin a manner such that the obstruction is between the first and secondblocking means, and the third location is located in proximity to theobstruction;

causing the blocking means to block blood flow around the catheterswhile blood continues to flow through the blood bypass flow path; and

delivering a dissolution agent to the obstruction via the dissolutionagent flow path.

The device according to the invention will be described with referenceto clot dissolution but could also be employed to deliver a plaquedissolving or fibrin dissolving substance to a blockage or obstruction.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side view of a first embodiment of a device according to thepresent invention.

FIG. 2 is a side cross-sectional view of sections of the distal portionof one catheter of FIG. 1, to a larger scale, taken along line II--II ofFIG. 3.

FIG. 3 is a transverse, or axial, cross-sectional view taken along theline III--III of FIG. 2.

FIG. 3a is a view similar to that of FIG. 3 showing the other catheterof FIG. 1.

FIG. 4 is a side view, partly in cross section, of a second embodimentof a catheter according to the invention.

FIG. 5 is a side view, partly in cross section, of a third embodiment ofa catheter according to the invention.

FIG. 6 is a side view of the distal end of a catheter according to thepresent invention.

FIG. 7 is a side view similar to FIG. 1 showing a modified form of onecomponent of a device according to the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

In order to dissolve a clot, for example, it is necessary to bring asuitable clot dissolution, or thrombolytic, agent into contact with theclot, one substance which presently finds wide use being urokinase.Referring to FIG. 1, in order to deliver such agent to the clot site,catheter 2 is provided with an axial lumen 8 (FIG. 3) whose distal endterminates in a comparatively large outlet opening 10. The proximal endof lumen 8 (not shown) would extend outside of the patient's body and beconnected to a suitable source of the dissolution agent.

Good medical practice generally dictates that the quantity of anyforeign substance introduced into a patient's body be no more than thatrequired to produce the intended result, whereby side effects can beprevented or at least minimized. In order to minimize the quantity ofclot dissolution agent employed to remove a clot, the device accordingto the present invention will serve to block the blood vessel at alocation downstream of the clot so that the dissolution agent introducedvia lumen 8 and outlet opening 10 will be confined to the region of theclot. Since the dissolution agent will be substantially prevented fromflowing away from the clot site, it will be appreciated that thisarrangement allows the quantity of substance introduced into the body tobe maintained at the minimum amount needed to produce the desiredresult.

A more specific goal of the present invention is to efficientlyeliminate clots or other obstructing materials by the action of adissolution agent which works in conjunction with certain bloodcomponents, e.g., enzymes, to effect dissolution.

The speed of the dissolving action is influenced by the quantitativerelation between the dissolution agent and the cooperating bloodcomponent and a given dissolution reaction will be optimized bymaintaining this relation in a given range. According to this invention,optimization can be achieved by controlling the flow rate of dissolutionagent to the clot site, controlling the quantity of blood at the clotsite, and monitoring the resulting chemical composition at the clotsite. The proportion of dissolution agent at the clot site is furthercontrolled to prevent or minimize injury to the blood vessel wall.

FIG. 1 shows the distal end portion of a device according to theinvention composed of, in addition to, infusion catheter 2, a suctioncatheter 3 in position in a blood vessel 4. A principal application ofthe present invention is the removal of clots in coronary arteries.Catheter 2 may be tapered at its distal end 5 to facilitate insertionand advance to the site of a clot.

Catheter 2 is provided with a plurality of lumens and lateral openingswhich perform various functions in a clot dissolution procedure. Theinternal structure of catheter 2 is illustrated more fully in FIGS. 2and 3, to which reference will now be made together with FIG. 1.

Because a separate catheter 3 is employed to perform the suctionoperation, the suction lumen in catheter 3 can be made larger than asuction lumen which might otherwise be provided in catheter 2.

According to one embodiment of the present invention, the clot site invessel 4 may be blocked by a balloon 12 fixed to the peripheral wall ofcatheter 2 and a balloon 13 fixed to the peripheral wall of catheter 3,each balloon having an inflation opening for the introduction ofinflation air via a lumen and an outlet opening of its respectivecatheter. In FIG. 2, a lumen 16 and outlet opening 18 for balloon 12 areshown. Balloons 12 and 13 are shown in their inflated state in FIG. 1and balloon 12 is shown in its deflated state in FIG. 2.

As is apparent from FIGS. 1 and 2, balloons are constructed such thatthe inflation opening of each balloon is attached to a small portion ofthe periphery of the associated catheter and each balloon expandseccentrically relative to the longitudinal axis of its catheter. This isparticularly desirable with regard to catheter 2, which is normallyinserted first, because expansion of balloon 12 will urge catheter 2toward the wall of vessel 4 leaving a relatively large free space forinsertion of catheter 3. On the other hand, balloon 13 may be eccentric,as shown, or concentric, i.e., in the form of an annular cuff.

While embodiments are conceivable in which both balloons 12 and 13 arecarried by catheter 2, in which case inflation of balloon 13 would beeffected via a separate lumen and outlet opening, the mounting ofballoon 13 on catheter 3 offers the advantage of permitting variation ofthe length of the blood vessel region enclosed by the balloons.

In the case where the obstructing material is close to a branching bloodvessel, as shown at 14 in FIG. 1, balloon 13 can be positioned toisolate the branching vessel from the treatment site. Alternatively, anattempt can be made to move the obstruction away from the branchingvessel by displacing one of the catheters with its balloon inflated.However, it may be necessary to insert a separate balloon catheter intothe branching vessel in order to block flow in that vessel.

As an alternative to a balloon, or balloons, any other known devices canbe employed to obstruct blood flow downstream of the clot site, suchdevices including, for example, filters or sponges. Such devices shouldbe constructed, however, to urge catheter 2 toward the wall of vessel 4.

The peripheral wall of catheter 2 is provided with two radiopaquemarkers 22 and 24 which are spaced apart by a distance sufficient tostraddle the site of a clot. Typically, the distance between markers 22and 24 could be of the order of 2 cm and these markers could, forexample, be in the form of annular bands. Passage 10 is locatedessentially midway between markers 22 and 24 and balloon 12 is locatedbetween distal marker 24 and distal end 5.

When catheter 2 is properly positioned at the site of a clot and balloon12 and/or 13 are inflated so as to block blood flow in vessel 4, it isdesired to maintain a flow of blood past the clot and this is achieved,according to the present invention, by providing catheter 2 with afurther lumen 26 having associated inlet openings 28 and outlet openings30. Preferably, lumen 26 is given as large a diameter as is permitted bythe available cross section of catheter 2 and the number of inletopenings 28 and outlet openings 30 is selected to provide a sufficientlylow flow resistance. At the outlet end, lumen 26 extends completely todistal end 5 of catheter 2 and will serve the additional function ofaccommodating a guide wire during insertion of the catheter, as will bedescribed below. However, particularly if end 5 is tapered, the outletend of lumen 26 could present an unacceptably high flow resistance.Outlet openings 30 overcome this difficulty.

As is illustrated, openings 28 and 30 are located so that blood flowingthrough lumen 26 will bypass balloon 12, as well as the site of theclot, when catheter 2 is properly positioned. By way of example, thespacing between openings 28 and radiopaque marker 22 could be of theorder of 4 cm. Balloon 13 will be positioned so that openings 28 willalways be located to be more remote from the distal end of the catheterthan is balloon 13.

Lumen 26 is further associated with a dye outlet opening 32 which islocated upstream of openings 28 and via which a suitable radiopaque dyemay be delivered to the clot region in order to assist X-ray observationof the positioning of catheter 2. By making opening 32 sufficientlylarge, dye delivered via the proximal end of lumen 26 will flowessentially entirely through opening 32, both because that opening willpresent a substantially lower flow resistance than will the downstreamportion of lumen 26, and because the dye will be entrained in bloodflowing through the vessel around catheter 2. During this time, balloon12 is not yet inflated and either catheter 3 is not yet inserted or itsballoon 13 is not inflated.

If catheter 2 is intended to be inserted into a vessel in the directioncounter to blood flow, dye could be delivered via a further lumen (notshown) having outlet opening 32 disposed between distal end 5 and outletopening 10, or a separate dye-delivery catheter could be employed.

The injection of dye or other observable agent, together withobservation of its behavior in the blood vessel, allows the positioningof catheters 2 and 3 and the appropriate inflation states of balloons 12and 13 to be determined. For example, if the dye flows off via a sidebranch, such as branch 14 in FIG. 1, catheter 13 may have to bedisplaced or a separate balloon may be required in the side branch. Thedirection of flow of the dye can indicate which balloon will have to bedeflated to admit additional blood to the treatment site. If the dyeremains in place, it may be possible to perform the treatment withoutinflating the balloons.

FIG. 3 shows, in axial cross section, one suitable arrangement of lumensin catheter 2. These can include a lumen 38 and an outlet opening 40 fordelivering inflation air to balloon 13 if that balloon is carried bycatheter 2. Similarly, FIG. 3a shows catheter 3 having a large areasuction lumen 3' and a balloon inflation lumen 3".

A clot removal operation according to the present invention could becarried out by the following procedure, which incorporates conventionalinsertion techniques. The procedure to be described by way of example isintended to remove a clot which has been found to be present in acoronary artery, and consists of the following sequence of steps:

1) A needle is inserted into the artery from outside the body, onelocation currently used being in the patient's groin.

2) A guide wire is inserted through the needle and into the artery to adistance possibly of the order of 10 cm.

3) The needle is then removed.

4) A sheath is slid around the guide wire and into the artery.

5) A guiding catheter is placed around the guide wire and into thesheath, the guiding catheter is advanced into the coronary artery, andthe sheath is removed from the artery.

6) The guide wire is then advanced through the guiding catheter and thenpast the distal end of the guiding catheter and across the site of theclot.

7) The guiding catheter is then withdrawn from the artery.

8) Then, infusion catheter 2 having the form shown in FIGS. 1-3 isplaced over the guide wire, i.e., lumen 26 is threaded around the guidewire and catheter 2 is advanced to the site of the clot, the position ofcatheter 2 being observable by the effect of X-rays on markers 22 and24.

9) When it appears that catheter 2 is at least approximately correctlylocated, the guide wire may be withdrawn and a suitable dye isintroduced via lumen 26 and opening 32 into the blood stream in order toallow X-ray observation of the clot and behavior of the dye and topermit final positioning of catheters 2 and 3.

10) When it is determined that catheter 2 has been properly positioned,eccentric balloon 12 is inflated in order to block one side of theregion which is the site of the clot and to urge catheter 2 to one sideof the artery.

11) Suction catheter 3 is then inserted and advanced to the treatmentsite, if necessary by a procedure as outlined at 1)-8). At this time, anattempt can be made to withdraw the clot simply by applying suction viacatheter 3. After an appropriate interval, balloon 12 may be deflatedand dye introduced via opening 32 to permit observation of the status ofthe clot.

12) If the clot is not removed in step 11), normally balloons 12 and 13will be inflated and thrombolytic agent is introduced, via lumen 8 andopening 10, at a rate sufficient to establish a sufficient concentrationthereof at the treatment site. Fluid is withdrawn from the treatmentsite via catheter 3 and its composition is analyzed. If theconcentration of thrombolytic agent is low, the delivery rate thereof isincreased, or the downstream balloon is inflated if it was previouslydeflated; if it is high, the delivery rate may be decreased and/or theupstream balloon is partially deflated to allow an additional quantityof blood to enter the treatment site. Suction is established, possiblyafter a selected dissolution time, to remove dissolved material andresidual clot particles. After a selected suction period, the balloonsmay be deflated and additional dye introduced to observe that status ofthe treatment site. If necessary, the entirety of this step is repeated.

Thus, according to the invention, dissolution agent may be confined tothe region between balloons and is prevented from flowing off into theremainder of the circulatory system. This means that the dissolutionagent is prevented from reaching regions of the circulatory system whichmay, because of disease or abnormality, cause serious harm to thepatient.

At the same time, the fluid composition at the clot site can be fullycontrolled in the manner described above.

One side of the clot site can be blocked by an eccentric balloon carriedby the infusion catheter or by a separate balloon carried by the suctioncatheter. In the latter case, the balloon carried by the suctioncatheter can be moved relative to the balloon carried by the infusioncatheter to adjust the length of the region blocked off by the balloons,and/or to close off a side branch adjacent the clot.

If the clot is too close to a side branch to allow the side branch to beisolated from the clot site, it may be possible to utilize the balloonwhich is adjacent the side branch to push the clot to a location whereit can be isolated from the remainder of the circulatory system.

For the majority of applications, catheter 2 may have a size of theorder of 4.5 to 7 French, a size of 5.5 French presently beingpreferred.

Two further embodiments of a catheter according to the present inventionare illustrated in cross section in FIGS. 4 and 5. Each of theseembodiments, like the embodiment of FIGS. 1-3, may be a unitary,extruded plastic member, the embodiments of FIGS. 4 and 5 beingconstructed to have a thin-walled design in order to provide relativelylarge flow passages. In this connection, priority should be given to thecross-sectional area of the blood bypass flow path since the maximumpossible flow rate along this path can prove beneficial to the patient.

FIG. 4 illustrates a catheter 50 having a basically cylindrical form andan internal configuration which provides a lumen 52 defining a bloodbypass flow path occupying substantially more than one-half of thecatheter interior cross section. Along the upper portion of catheter 50,there is provided a lumen 54 defining a thrombolytic agent flow pathwhich will communicate with the region surrounding catheter 50 via aplurality of outlet passages 56 which replace the single large opening10 of the embodiment shown in FIGS. 1-3.

Finally, catheter 50 is provided with a balloon inflation lumen 58.

In this embodiment, the wall of lumen 58 projects radially slightlybeyond the basic circular outline of catheter 50 in order to permit thecross-sectional area of lumen 52 to be enlarged.

In the embodiment shown in FIG. 5, catheter 60 is formed to have a stilllarger blood bypass flow lumen 62 by constructing the thin-walledstructure of catheter 60 to have a radially protruding portion 64 whichencloses a lumen 66 for delivering thrombolytic agent. Because of theradially protruding position of portion 64, the outlet end of lumen 66can be provided with a number of outlet openings 68. Catheter 60 iscompleted by a balloon inflation lumen 70 corresponding essentially tolumen 58 of FIG. 4.

In each of the embodiments illustrated in FIGS. 4 and 5, a secondballoon inflation lumen may be provided at any desired location if thecatheter is to carry the second balloon 13 which is to be separatelyinflated. In addition, the catheters according to these embodiments canhave a tapered distal end, as shown for the embodiment of FIGS. 1-3, andlumens 52 and 62 will extend the entire length of the catheter to servethe additional function of accommodating a guide wire.

Further, in the embodiments of FIGS. 4 and 5, a radiopaque dye may bedelivered to the region of the clot via the blood bypass flow lumen 52,62, in a manner similar to that described above with reference to FIGS.1-3. Specifically, lumen 52, 62 can extend fully to the proximal end ofthe catheter and, at a location upstream of the blood bypass flowregion, this lumen may be provided with a large opening or an array ofopenings via which all or substantially all of a dye introduced via theproximal end of the catheter will exit into the blood stream. When nodye is being delivered, this opening or openings may serve as additionalblood bypass flow inlet openings.

In each embodiment of the present invention, the inlet and outletopenings for the blood bypass flow path may be constituted by an arrayof openings 72, as shown in FIG. 6. This array may be distributed aroundone-half of the circumference of the catheter or, in the embodiments ofFIGS. 4 and 5, may be provided in both halves of the circumference ofthe catheter, outside of the regions occupied by the other lumens, 54,58, 66, 70. Openings 56 and 68 may also be distributed to have the formof array 72.

According to a further feature of the invention, catheter 3 may beprovided with a balloon 13' which, upon inflation, assumes an oblongconfiguration, or is elongated in the longitudinal direction, as shownin FIG. 7. Such a balloon, which can be fabricated according toprinciples known in the balloon fabrication art, has an enhancedcapability of blocking blood vessel side branches immediately adjacentthe treatment site. If balloon 13' is provided, it may be necessary toplace openings 28 and 32 at a greater distance from distal end 5 ofcatheter 2.

Another characteristic of the embodiment of FIG. 7 is that balloon 13'is configured to expand symmetrically around catheter 3. This permitsballoon 13' to effectively block side branches at any location aroundthe circumference of vessel 4.

While a preferred embodiment of a device according to the invention hasbeen described and illustrated, it will be appreciated that variousrearrangements of the component parts can be made without departing fromthe spirit and concept of the invention. Thus, as already mentioned,balloon 13 or 13' could be carried by infusion catheter 2.Alternatively, catheter 2 could carry a single balloon at the locationof balloon 13, instead of at the location of balloon 12, particularlyif, for any reason, it is desirable or necessary to insert catheter 3from the direction opposite to that of catheter 2.

A treatment procedure according to the invention could further includeintroduction of an observation device to the treatment site.

As an alternative to the embodiments described above, embodiments of theinvention may include but a single eccentric balloon, preferably mountedon infusion catheter 2. This arrangement may prove preferable fordealing with certain anatomical conditions encountered in thecirculatory system. Depending on the conditions existing at thetreatment site, relating to the actual blood flow pattern and the natureof the obstructions in the vicinity of the treatment site, the singleballoon may be either at the distal location of balloon 12 or at theproximal location of balloon 13. Such an alternative arrangement wouldbe utilized in situations where it is still possible to satisfy the goalof maintaining the desired quantity of dissolution agent and the desiredproportion of blood at the treatment site by appropriate control of thedissolution agent delivery rate and the suction rate, whilesubstantially preventing any significant flow of the dissolution agentaway from the treatment site and through the remainder of thecirculatory system.

While the description above refers to particular embodiments of thepresent invention, it will be understood that many modifications may bemade without departing from the spirit thereof. The accompanying claimsare intended to cover such modifications as would fall within the truescope and spirit of the present invention.

The presently disclosed embodiments are therefore to be considered inall respects as illustrative and not restrictive, the scope of theinvention being indicated by the appended claims, rather than theforegoing description, and all changes which come within the meaning andrange of equivalency of the claims are therefore intended to be embracedtherein.

What is claimed:
 1. A method of dissolving an clot in a blood vessel,comprising:preventing blood which is in contact with the clot fromflowing through the vessel to locations downstream of the clot whilepermitting blood to flow through a passage past the clot; delivering tothe clot a dissolution agent which works in conjunction with bloodcomponents to effect dissolution of the clot, so that a fluid whichincludes the dissolution agent and blood is in contact with theobstruction; withdrawing a sample of the fluid, which includes portionsof dissolved clot material, from the blood vessel; directly determiningthe composition of the fluid in the sample; and adjusting theconcentration of dissolution agent in the fluid in contact with the cloton the basis of the result of said determining step.
 2. A method asdefined in claim 1 wherein said step of adjusting comprises supplyingblood to the fluid in contact with the clot.
 3. A method as defined inclaim 1 wherein said step of adjusting comprises increasing the quantityof dissolution agent in he fluid in contact with the clot.
 4. A methodas defined in claim 1 wherein the concentration of dissolution agent inthe fluid in contact with the clot has an optimum range of values, andsaid step of adjusting comprises supplying blood to the fluid in contactwith the clot when said determining step indicates that theconcentration of dissolution agent in the fluid in contact with the clotis higher than the optimum range, and increasing the quantity ofdissolution agent in the fluid in contact with the clot when saiddetermining steps indicate that the concentration of dissolution agentin the fluid in contact with the clot is lower than the optimum range.5. A method as defined in claim 4 wherein said steps of determining andadjusting are performed a plurality of times in the recited order.
 6. Amethod as defined in claim 1 wherein said steps of determining andadjusting are performed a plurality of times in the recited order.